Cellular therapy using stem cells derived from the bone marrow and cardiac origin are validated to treat damage after myocardial infarction (MI) in both small animal models and human clinical trials. The use of cellular therapy to treat MI has been largely unsatisfactory, with many protocols showing little to no improvement in cardiac function after long-term follow up studies. The inherent limitation of autologous stem cell therapy is that cells derived from aged organs have increased expression of senescent markers and acquisition of chromosomal abnormalities leading to undesirable cellular characteristics such as slowed proliferation and increased susceptibility to cellular death. Furthermore, based on animal models, cellular survival and engraftment is hindered by adverse inflammation, inhibiting the ability of transplanted stem cells to efficiently differentiate into cardiac cells. Improvement of stem cell engraftment and survival has been attempted by co-injection of stem cells with biomaterials, cytokines and growth factors, or by genetically enhancing cells with pro-survival and anti-apoptotic genes.
The heart is capable of limited regeneration, as evidenced by cardiomyocyte re-entry into the cell cycle and production of new mono-nucleated myocytes during aging and after pathological damage. New myocyte formation is partially due to reserve c-kit+ cardiac progenitor cells (CPCs) found in complex microenvironments or niches. In vivo, CPCs retain expression of primitive cardiac transcription factors and upon activation can give rise to cells of the cardiac lineages.
The regenerative potential of stem cells in a clinical setting is still largely unrecognized. Although stem cells are suggested to function through a variety of mechanisms for myocardial repair, in practice stem cells have been inherently limited because of origin and potency status.